This research has three specific objectives: (1) Chemotherapeutic studies of M. leprae-infected, neonatally thymectomized Lewis rats (NTLR), which will be used as models of multibacillary leprosy. Our goals are (a) to investigate a variety of drug regimens for their ability to eradicate m. leprae infection and (b) to utilize NTLR for the early detection of the persister state. This will be done by passage of M. leprae from drug-treated NTLR into intact mice and NTLR. (2) Development of the athymic nude rat as a model of lepromatous leprosy. The objectives is to characterize the infection resulting from the inoculation of M. leprae to determine whether the athymic rat is sufficiently immunosuppressed and long-lived to replace the NTLR in the studies outlined above. The gene for athymia will be placed on a Lewis rat background in order to obtain a uniformly susceptible animal. (3) Tissue culture and morphological studies by electron microscopy of M. leprae. These studies will involve attempts to cultivate M. leprae in human skin epithelial cells grown on collagen gels. Infected cells will be examined by electron microscopy with the aim of determining whether we can correlate the morphological status of the M. leprae in situ with viability.